PROJECT SUMMARY/ABSTRACT This is a proposal for the renewal of a training grant, the primary purpose of which is to provide stipends for five predoctoral and three postdoctoral fellows who will be broadly and intensively trained to conduct research on the neurobiological and behavioral effects of alcohol. This program has a long history of training predoctoral and postdoctoral students in alcoholism research to help the national effort of producing the next generation of independent scientists with a focus on alcohol research. Training opportunities span the breadth of state-of- the-art approaches including molecular biology and genetics, electrophysiology, cellular imaging, neurochemistry, and behavior. Research models include both animal and human. The training program will promote and support collaborative research across multiple departmental units and Ph.D. programs including Clinical Psychology, Behavioral Neuroscience, Pharmacology, Neuroscience, and Cellular and Molecular Biology. Molecular biology training will encompass 1) studies of the function of excitatory and inhibitory ion channels in cellular expression systems (Mihic, Harris), 2) development of new transgenic animal models (Messing, Harris, Mihic, Pierce-Shimomura, Atkinson), and 3) identification of ethanol responsive genes (Atkinson, Harris, Mihic, Pierce-Shimomura). Genetics training will involve genotyping of human and animal subjects (Fromme, Harris, Mayfield, Ponomarev). Electrophysiological and microscopic imaging training will comprise experiments with whole cell and intracellular methods in single cells and in brain slices (Morrisett, Mihic, Harris, Atkinson, Pierce-Shimomura, Messing, Marinelli). Training in neurochemistry will focus on 1) intracellular and extracellular signaling mechanisms with an emphasis on phosphorylation (Morrisett, Mayfield), 2) release and transport of glutamate, dopamine, and other neurotransmitters (Gonzales, Harris, Dominguez), and 3) expression of proteins (Harris, Mayfield, Morrisett, Messing). Research on the behavioral effects of ethanol will include its influence on motor skills, reinforcement, anxiety, and withdrawal (Harris, Gonzales, Dominguez, Morrisett). Training in psychosocial aspects of alcohol research (Fromme) and the interaction of genotype and effects of alcohol drinking in humans (Fromme, Harris) will also be done. The training program will continue to emphasize professional development including improvement of oral and written communication skills and grant writing. Predoctoral students will be required to complete a series of core course requirements, scientific ethics, experimental design, and statistical analysis, and will end up with a Ph.D. degree. Postdoctoral training will be for three years and consist of focused alcohol research guided by a faculty mentor. We will continue to focus on minority recruitment. The training faculty has an excellent history of collaboration with a primary focus on alcohol research. The research laboratories are well equipped with the latest instrumentation for neurochemical and behavioral testing.